An oral administration using a tablet, a capsule, a syrup, or the like has been performed as a method of administration of a drug for various kinds of medicaments. However, the oral administration has included drawbacks such as insufficient sustainability of a drug effect and the fact that a concentration of a drug in blood is temporarily increased to an excessive level after the administration, and hence an adverse side effect is likely to occur. In order to eliminate such drawbacks involved in the oral administration, development of a transdermal preparation, particularly, a tape preparation in which an adhesive matrix layer containing a drug is provided on one surface of a support such as a plastic film has been carried out. The tape preparation is expected not only to compensate those drawbacks but also to exhibit advantages such as decreasing the number of administration, improving compliance, ease of administration, and ease of stopping the administration. Further, the tape preparation is known to be more useful for elderly patients and child patients. Moreover, the tape preparation sustains a preparation function even after cutting unlike a reservoir-type preparation, and hence adjusting the dose of administration (area) depending on the age and body size of a patient is easy.
However, most drugs generally have low skin permeability, and hence the development of a transdermal preparation is difficult. The structure of skin is mainly formed of epidermis, dermis, and subcutaneous tissue. The outermost side of epidermis is covered with dead and keratinized cells having a thickness of 10 to 15 μm called a stratum corneum. The stratum corneum functions as a preventive barrier against the inflow and outflow of chemicals including drugs and water evaporation. That is, the rate-limiting step of percutaneous absorption lies in a process of permeating a corneum, and hence, in the case of the development of a tape preparation, enhancing the drug permeability into the stratum corneum has been the most important issue.
Thus, in order that the barrier function of the stratum corneum may be weakened in order for the stratum corneum to absorb a sufficient amount of drugs, studies on percutaneous absorption enhancers have been widely carried out. Examples of the percutaneous absorption enhancers include: fatty acids, fatty alcohols, fatty acid esters, fatty acid amides, and fatty acid ethers each having 6 to 20 carbon chains; aromatic organic acids, aromatic alcohols, aromatic organic acid esters, and aromatic organic acid ethers; and further, lactates, acetates, monoterpene-based compounds, sesquiterpene-based compounds, azone, azone derivatives, pyrrothiodecane, glycerol fatty acid esters, propylene glycol fatty acid esters, sorbitan fatty acid esters, polyethylene glycol fatty acid esters, polyoxyethylene hardened castor oils, polyoxyethylene alkyl ethers, sucrose fatty acid esters, and vegetable oils. Further, surfactants such as alkyl glycosides are also known to be used as percutaneous absorption enhancers (see, for example, Patent Literature 1 and Non Patent Literature 1).
On the other hand, in order to obtain a tape preparation, in addition to the percutaneous absorbability of drugs, providing a good balance among requirements such as (1) drugs are released well from an adhesive layer, (2) drugs are transferred into skin for a long time, (3) adhesiveness to the surface of skin is preferable, (4) neither a residual glue on the surface of skin nor cobwebbing occurs at the time of detachment, and (5) irritation to skin is slight, should be necessary. Thus, in the case of the development of the tape preparation, it has been conventionally necessary to study, for example, the chemical properties and physical properties of a target drug, an adhesive base, a percutaneous absorption enhancer, and other components, and interactions caused by a combination of the target drug with other substances. As a result, only particularly limited drugs such as isosorbide dinitrate, nitroglycerin, scopolamine, estradiol, and tulobuterol have been put to practical use for the purpose of systemic administration.
In order to obtain a matrix-type preparation, the percutaneous absorption enhancer should not only exhibit a sufficient percutaneous absorption enhancing action to a drug, but also have excellent compatibilities with an adhesive base and other additives and not affect the agglomerating property, and adhesiveness to the surface of skin, of an adhesive layer. However, until now, there has been no percutaneous absorption enhancer obtained by studying various drugs and various adhesive bases from the above-mentioned viewpoint. There has been therefore demanded a practical percutaneous absorption enhancer that enhances percutaneous absorption of a wide range of drugs, is excellent in compatibility with various adhesive bases, and does not affect the agglomerating property, and adhesiveness to the surface of skin, of an adhesive layer.